Arhiv Za Higijenu Rada I Toksikologiju-Archives of Industrial Hygiene and Toxicology最新文献

Polymyxin antibiotics are the last resort for treating patients in intensive care units infected with multiple-resistant Gram-negative bacteria. Due to their polycationic structure, their mode of action is based on an ionic interaction with the negatively charged lipid A portion of the lipopolysaccharide (LPS). The most prevalent polymyxin resistance mechanisms involve covalent modifications of lipid A: addition of the cationic sugar 4-amino-L-arabinose (L-Ara4N) and/or phosphoethanolamine (pEtN). The modified structure of lipid A has a lower net negative charge, leading to the repulsion of polymyxins and bacterial resistance to membrane disruption. Genes encoding the enzymatic systems involved in these modifications can be transferred either through chromosomes or mobile genetic elements. Therefore, new approaches to resistance diagnostics have been developed. On another note, interfering with these enzymatic systems might offer new therapeutic targets for drug discovery. This literature review focuses on diagnostic approaches based on structural changes in lipid A and on the therapeutic potential of molecules interfering with these changes.

Antineoplastic drugs (ADs) are essential tools in cancer treatment, but their cytotoxicity poses a risk to workers involved in their handling. In a hospital environment fundamental strategies for minimising exposure involve proper use of safety cabinets and closed-circuit transfer devices, along with personnel training and increased awareness of risks. However, medical gloves remain the first line of defence. In this respect the evaluation of glove materials and best choices can improve hospital safety management and prevent potential hazards and long-term consequences. The aim of this study was to assess contamination of gloves in samples taken from AD administration and preparation units of nine Italian hospitals and to raise awareness of the importance of evaluating chemico-physical properties of gloves. Our findings show that 33 % of the analysed gloves were positive for at least one AD, with contaminations ranging from 0.6 to 20,729 pg/ cm². We proposed the alert glove values (AGVs) for each AD as a limit value for contamination assessment and good practice evaluation. Our findings also point to multiple AD contamination (43 % of positive findings in preparation units), calculated as total AGV (AGV-T), and confirm that gloves should be replaced after 30 min of AD handling, based on cumulative permeation and area under the curve (AUC), to maintain safety and limit dermal exposure.

Girdin is a protein involved in neuronal migration and hippocampal development. It is encoded by the coiled-coil domain-containing 88A (CCDC88A) gene, located on the short arm of chromosome 2 (2p). The CCDC88A gene is modulated by the intergenic single-nucleotide polymorphism (SNP) of the rs1437396, situated 9.5 kb downstream from its transcription stop site. As recent genome-wide research has associated the T allele of the SNP with increased risk of alcohol use disorder (AUD), we wanted to validate this finding in an independent cohort and to test further for an association with comorbid major depressive disorder (MDD). The study included 226 AUD patients (AUD group), 53 patients with comorbid MDD, and 391 controls selected randomly. The participants were genotyped for the rs1437396 polymorphism using the real-time polymerase chain reaction. The association between the rs1437396 polymorphism and increased risk of AUD and AUD+MDD was tested with logistic regression. Our results show significantly higher frequency of the T risk allele in the AUD group (p=0.027) and even higher in the AUD+MDD group (p=0.016). In conclusion, this is the first study that has validated the association between the rs1437396 polymorphism of the CCDC88A gene and AUD with or without MDD. Studies on larger samples of patients are needed to further investigate the mechanism of this association.

Occupational and environmental toxicology specialists find catecholamine fluctuations in brain tissue relevant for research of neurotoxicity, such as that induced by manganese or zinc, pesticides, industrial solvents, plastic, air pollution, or irradiation. Considering that catecholamine tissue concentrations are generally very low, their extraction requires a reliable and optimal method that will achieve maximum recovery and minimise other interferences. This study aimed to evaluate whether the aluminium (III) oxide (Al₂O₃, alumina) based cartridges designed for catecholamine isolation from plasma could be used for solid-phase extraction (SPE) of catecholamine from the brain tissue. To do that, we homogenised Wistar rat brain tissue with perchloric acid and compared three extraction techniques: SPE, the routine filtration through a 0.22 µm membrane filter, and their combination. In the extracts, we compared relative chromatographic catecholamine mobility measured with high performance liquid chromatography with electrochemical detection. Chromatographic patterns for norepinephrine and epinephrine were similar regardless of the extraction technique, which indicates that the alumina cartridge is good enough to isolate them from brain tissue. However, the dopamine pattern was unsatisfactory, and further experiments are needed to identify the issue and optimise the protocol.

Silver nanoparticles (AgNPs), which have recently gained attention due to their antimicrobial activity, can also be produced by green synthesis. The aims of this study were to (i) characterise green synthesized AgNPs using microwave-assisted aqueous extracts of Galium aparine (G-AgNPs) and Helichrysum arenarium (H-AgNPs) and (ii) investigate the combined antimicrobial effects of the G- and H-AgNPs in different ratios. Nanoparticle formation and reactions were determined with UV-Vis spectroscopy. The G-AgNPs were 52.0±10.9 nm in size, with a 0.285±0.034 polydispersity index (PDI), and a -17.9±0.9 mV zeta potential. For H-AgNPs these characteristics were 23.9±1.0 nm, 0.280±0.032, and -21.3±2.7 mV, respectively. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) confirmed that the particles were monodisperse and spherical. The Fourier transform-infrared spectroscopy (FT-IR) results showed the presence of reducing agents that stabilised the AgNPs. Three different nanoformulations (NF-1, NF-2, and NF-3) were prepared by combining these two synthesised nanoparticles in different ratios and their antimicrobial activity was tested against E. coli, S. aureus, C. albicans, and A. flavus. Our study is the first to show that combining AgNPs from two different biological sources can produce effective nanoformulations with improved antibacterial activity against E. coli and S. aureus. These nanoformulations showed lower minimum inhibitory concentrations (31.25 µg/mL against E. coli with all NFs; 62.5 µg/mL for NF-1 and 125 µg/mL for NF-2/3 against S. aureus) than G-AgNPs (62.5 µg/mL for E. coli) or H-AgNPs (125 µg/mL for S. aureus) alone. Their high combined inhibitory effect against E. coli (NF-1-3) was synergistic and against S. aureus (NF-2 and NF-3) potentially additive. Considering such promising results, we believe our study provides some direction for new research and strategies in antimicrobial therapeutics.

The burnout syndrome may affect academic achievement, but research on burnout and academic success of medical students is sparse. This research aimed to estimate the prevalence of high risk of burnout in students of medicine and to investigate its association with academic performance. It included 760 full-time medical students who completed the survey (response rate = 90.9 %). A significant independent predictor for high burnout risk in students with lower grade point average (GPA) was male gender (adjusted OR=2.44; 95 % CI=1.14-5.23; P=0.022). Among students with higher GPA, high burnout risk was associated with the use of sedatives (adjusted OR=6.44; 95 % CI=1.80-22.99; P=0.004).

Ketamine is a dissociative anaesthetic used to induce general anaesthesia in humans and laboratory animals. Due to its hallucinogenic and dissociative effects, it is also used as a recreational drug. Anaesthetic agents can cause toxic effects at the cellular level and affect cell survival, induce DNA damage, and cause oxidant/antioxidant imbalance. The aim of this study was to explore these possible adverse effects of ketamine on hepatocellular HepG2 and neuroblastoma SH-SY5Y cells after 24-hour exposure to a concentration range covering concentrations used in analgesia, drug abuse, and anaesthesia (0.39, 1.56, and 6.25 µmol/L, respectively). At these concentrations ketamine had relatively low toxic outcomes, as it lowered HepG2 and SH-SY5Y cell viability up to 30 %, and low, potentially repairable DNA damage. Interestingly, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) remained unchanged in both cell lines. On the other hand, oxidative stress markers [superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)] pointed to ketamine-induced oxidant/antioxidant imbalance.

The aim of this study was to investigate the effects of resveratrol against fumonisin B₁ (FB₁)-induced liver toxicity, as, to the best of our knowledge, these effects have not been investigated yet, even though the toxic effects and mechanisms of FB₁ and the antioxidative effects of resveratrol are well known. 40 BALB/c mice were divided into control, FB₁, resveratrol, and FB₁+resveratrol groups. Control received saline for 14 days. The FB₁ group received 2.25 mg/kg FB₁ every other day for 14 days. The resveratrol group received 10 mg/kg resveratrol for 14 days. The FB₁+resveratrol group received 2.25 mg/kg FB₁ every other day and 10 mg/kg resveratrol every day for 14 days. All administrations were peritoneal. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total sialic acid (TSA) levels were analysed in serum samples, while total antioxidant status (TAS) and total oxidant status (TOS) were measured in the liver. Additionally, the liver tissue was examined for histopathological changes. AST, ALT, and TSA were significantly higher in the FB₁ group than control. Resveratrol countered FB₁ effects for all parameters, including TOS and TAS. Liver histology showed FB₁-induced hyperaemia, infiltrations, and megalokaryosis in some hepatocytes. No pathological findings were detected in the control, resveratrol, or FB₁+resveratrol group. Our findings confirm resveratrol's protective effect against liver damage and oxidative stress caused by FB₁. In addition, they suggest that increased serum TSA levels can be used as a biomarker of FB₁-induced hepatotoxicity.